Project Summary Childhood obesity is a critical public health problem that affects approximately 12.5 million children and teens in the United States. In our current obesogenic environment, children frequently have access to highly palatable foods such as packaged foods containing high levels of sugar, salt and fat. Importantly, most children will continue to consume highly palatable foods, even after they have eaten to satiety. This excess consumption, termed eating in the absence of hunger (EAH), is associated with child weight gain. The overarching hypothesis of the present study is that some children are genetically predisposed to EAH in response to environmental food cues, and further that self-regulatory capacity can protect children from this reward-driven overeating. The proposed aims are a major expansion of our preliminary study (1R21HD076097) in 9-10 year olds (n=172) that provides initial evidence that obesity risk alleles in the fat mass and obesity-associated (FTO) gene relate to greater EAH and brain reward-region activity in response to food cues. Our initial exploratory award led to intriguing findings that raise a number of new exciting questions and research directions. In our current expanded study, we will directly assess whether food-cue-related neural activity relates to cued EAH and adiposity gain?an outcome with critical public health significance. We will also incorporate a robust measure of self-regulatory capacity to study how this modifiable trait influences the association between neural reward activity with EAH and subsequent adiposity gain. Our expanded research will also advance our understanding of the biological mechanisms by which adiposity is affected by other known genetic obesity risk factors like melanocortin 4 receptor (MC4R) gene. This expanded study uses a comprehensive, multidisciplinary approach to increase our understanding of how genetic factors interact with environmental food cues to affect obesogenic eating behaviors in children. Most children have a very high daily exposure to external food cues. In addition to smelling and seeing actual food throughout the day, many children also experience numerous food cues in the form of TV and Internet food advertisements (ads) that can prompt cravings and EAH. Indeed, food manufacturers spend approximately 1.8 billion dollars a year marketing highly palatable foods to children under 12 years old through methods such as TV ads, Internet banner and pop-up ads, and Internet advergames. Thus, cued EAH could be an important driver of the child obesity epidemic. The study findings will have important implications for individualized child obesity intervention and prevention programs, and will also impact the public policy discourse on TV and Internet advertising of unhealthy foods to children. In a country where over one third of children are overweight or obese, it is essential to understand and systematically change environmental factors that lead to excess consumption.